The Digestive Diseases Research Core Center at the University of North Carolina seeks five years of additional support to study gastrointestinal biology and the pathophysiology of gastrointestinal diseases. In the first three of four years of Center funding under the initial award, four major areas of research have emerged in this Center: (1) intestinal water and electrolyte transport, (2) gastrointestinal inflammation and immunology, (3) gastrointestinal epithelial damage, growth, development and repair, and (4) gastrointestinal epidemiology. Interactive research among 34 Investigators from 15 Departments in 5 Schools located in two separate Universities (UNC-CH and NCSU) has been facilitated by two core laboratories (Barrier Intact Animal Facility at NCSU and Biostatistics Core at UNC-CH) and by a pilot/feasibility (P/F) program that has funded (in the first three years) 15 separate studies. Proposed changes in the Center for the next five years include: (1) changing the name from the Core Center in Diarrheal Diseases (CCDD) to the Center for Gastrointestinal Biology and Disease (CGIBD), (2) maintaining the Biostatistics Core, splitting the Barrier Intact Animal Facility into two cores (Gnotobiotic Animal Core and Barrier Intact Piglet Facility) and adding a Molecular Biology Core and an Immunoassay Core, (3) increasing the yearly amount of pilot/feasibility funding, and (4) adding nine new members to the Center with the purpose of further developing research in molecular biology. The unifying theme of research that has emerged from this Center is the study of the interaction between intestinal mesenchymal elements (immune cells, fibroblasts, endothelium and muscle) and the epithelial in the regulation of intestinal water and electrolyte transport, epithelial barrier functions and epithelial growth, development and repair. Proposed new P/F studies include investigation into: the expression of novel cytokines in the intestine in inflammatory bowel disease, the biochemistry of the intestinal extracellular matrix, mechanisms of intestinal potassium transport in rotavirus enteritis and the role of platelet activating factor as a neuromodulator of the enteric nervous system. The questions to be asked and answered by research in this Center are central to the prophylaxis and therapy of gastrointestinal acid-peptic diseases, cancer, infectious and functional diarrheas and inflammatory bowel disease.